JCI Insight (Jan 2021)

An immune-based biomarker signature is associated with mortality in COVID-19 patients

  • Michael S. Abers,
  • Ottavia M. Delmonte,
  • Emily E. Ricotta,
  • Jonathan Fintzi,
  • Danielle L. Fink,
  • Adriana A. Almeida de Jesus,
  • Kol A. Zarember,
  • Sara Alehashemi,
  • Vasileios Oikonomou,
  • Jigar V. Desai,
  • Scott W. Canna,
  • Bita Shakoory,
  • Kerry Dobbs,
  • Luisa Imberti,
  • Alessandra Sottini,
  • Eugenia Quiros-Roldan,
  • Francesco Castelli,
  • Camillo Rossi,
  • Duilio Brugnoni,
  • Andrea Biondi,
  • Laura Rachele Bettini,
  • Mariella D’Angio’,
  • Paolo Bonfanti,
  • Riccardo Castagnoli,
  • Daniela Montagna,
  • Amelia Licari,
  • Gian Luigi Marseglia,
  • Emily F. Gliniewicz,
  • Elana Shaw,
  • Dana E. Kahle,
  • Andre T. Rastegar,
  • Michael Stack,
  • Katherine Myint-Hpu,
  • Susan L. Levinson,
  • Mark J. DiNubile,
  • Daniel W. Chertow,
  • Peter D. Burbelo,
  • Jeffrey I. Cohen,
  • Katherine R. Calvo,
  • John S. Tsang,
  • NIAID COVID-19 Consortium,
  • Helen C. Su,
  • John I. Gallin,
  • Douglas B. Kuhns,
  • Raphaela Goldbach-Mansky,
  • Michail S. Lionakis,
  • Luigi D. Notarangelo

Journal volume & issue
Vol. 6, no. 1

Abstract

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Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (COVID-19). However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity and assessed type I IFN–, type II IFN–, and NF-κB–dependent whole-blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and nonhematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients’ first samples revealed 12 biomarkers (CCL2, IL-15, soluble ST2 [sST2], NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and 2 additional biomarkers (lactoferrin, CXCL9) that were substantially associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.

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